AB0093 MODELING OF ANTIGEN-COLLAGEN-INDUCED ARTHRITIS IN BALB/c MICE
Authors: M. Fisher, V. Kurilin, S. Sennikov
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Currently, disease-modifying drugs and biological agents are used to treat RA [1]. The available drugs are not perfect: they have serious side effects and do not always cause a stable improvement or remission [2]. The above sets the task of finding new approaches to treatment that will be effective, more specific and safe. In this connection, it is necessary to develop and apply experimental models as close as possible in pathogenesis to rheumatoid arthritis. One such model, rarely used at present, is the combined antigen-collagen-induced arthritis [3]. Objectives To show immunological and histological changes similar to RA in the AIA/CIA model and the validity of its application in research activities. Methods Experimental AIA/CIA was induced according to 2 different protocols in 50 BALB/c mice. Clinical assessment of arthritis was made by measuring the swelling of the paws with a caliper at different times. The assessment of immunological changes included the analysis of the content of antibodies to type II collagen by ELISA, the content of T-regulatory cells by flow cytometry. Also, a histological analysis of the obtained data was carried out. Results On the 10th day, a significant increase in paw thickness was recorded in animals induced both according to the first and second protocols. The intensity of swelling subsided by the 23rd day. A significant increase in the content of antibodies to type II collagen was observed in all experimental groups, but in animals from Protocol No. 1, the amount of antibodies to type II collagen was significantly higher. A high level of T-regulatory cells was registered only in mice induced according to the first protocol on the 10th day. Histological changes in the form of synovial hyperplasia, pannus, usurations were observed to varying degrees in all experimental groups, but the most pronounced changes were in animals from the first protocol. Conclusion In experimental animals, in all the presented protocols, changes were observed that were closest to RA, when compared with classical models of experimental arthritis induction. Based on the fact that protocol 1 animals showed an increase in the content of T-regulatory cells, the levels of antibodies to type 2 collagen were consistently high, and the histological changes were the most pronounced, it can be assumed that protocol 1 of the combined AIA/CIA model on the line of Balb/c mice, is the most suitable for testing and developing new methods of RA therapy. References [1]Abbasi M, Mousavi MJ, Jamalzehi S, Alimohammadi R, Bezvan MH, Mohammadi H, Aslani S. Strategies toward rheumatoid arthritis therapy; the old and the new. J Cell Physiol. 2019 Jul;234(7):10018-10031. doi: 10.1002/jcp.27860. Epub 2018 Dec 7. PMID: 30536757. [2]Greenberg JD, Reed G, Kremer JM, Tindall E, Kavanaugh A, Zheng C, Bishai W, Hochberg MC; CORRONA Investigators. Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry. Ann Rheum Dis. 2010 Feb;69(2):380-6. doi: 10.1136/ard.2008.089276. Epub 2009 Apr 8. PMID: 19359261; PMCID: PMC2861900. [3]Baddack U, Hartmann S, Bang H, Grobe J, Loddenkemper C, Lipp M, Müller G. A chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice. Nat Commun. 2013;4:1644. doi: 10.1038/ncomms2625. PMID: 23552059; PMCID: PMC3644064 Disclosure of Interests None declared